Novel advancements in lipids, polymers, and their hybrid nanoparticles, along with their applications for the biomedical sector, are discussed in a recent review published in the journal Pharmaceutics.
Study: New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery. Image Credit: Chokniti Khongchum/Shutterstock.com
Importance of Nucleic Acids
A plethora of therapeutic nucleic acids (TNAs) has opened opportunities for the sustainable development of innovative therapeutic approaches for various injuries, viral illnesses, and connective tissue disorders. These can aid the development of treatments and immunizations that stimulate a cell-mediated inflammatory system.
TNAs are gaining scientific attention because of the long-lasting benefits they provide compared to traditional therapies. Conventional medicine, in particular, produces only transient results since it targets proteins rather than the underlying factors.
TNAs, on the other hand, can have durable and potentially healing impacts through gene suppression, augmentation, substitution, or alteration.
Challenges Faced in the Past
Direct distribution of nucleotides has various limitations, including proteolytic degradation, controlled release, and low intracellular absorption due to difficulty penetrating cellular membranes. These difficulties are primarily due to TNAs' high molecular mass, negatively charged framework, and more delicate and allergenic capability than oligonucleotides.
As a result, therapeutic application of such medicines relies heavily on delivery strategies that must increase TNA durability, guard against extrinsic hydrolysis, enable cell uptake, and enhance targeted selectivity.
Lipid Nanoparticles Delivery Systems
Lipid nanoparticles (LNPs) have sparked substantial professional curiosity for enclosing TNAs, owing to the existence of electroactive lipids that are cationic at low pH, permitting complex formation with negatively charged RNA or DNA.
Customized LNPs can transfer RNA-based therapies to leukocytes, allowing for precise and comprehensive genomic modulation, making them an extremely promising therapy for many immune-related diseases.
TNAs can also be used in compositions to prevent and control heart diseases.
Another well-studied application of LNPs is the creation of COVID-19 vaccinations, with many preparations now in commercial use for mRNA distribution.
Applications of Polymer Nanoparticles Delivery Systems
Polyester resins have piqued the curiosity of researchers looking to create novel TNA transporters. This is because they can create electrostatic nanocomplexes with strongly negative nucleotides to enhance their absorption by specific cells.
On the other hand, other hydrophobic polymeric materials can effectively coerce TNAs between nanoparticles. Combining two or more polymeric materials in the same delivery mechanism is another intriguing potential.
Polymers have also been tried for TNA administration using microneedles. Furthermore, this novel delivery route elicited stronger humoral and cellular immune reactions than intravenous or intramuscular administration.
Lipid-Polymer Hybrid-based Delivery Systems
Lately, hybrid delivery mechanisms have emerged as a potential approach for circumventing the constraints of each particular lipid or polymer constituent. These delivery techniques outperformed non-targeted liposomal compounds in terms of transfection efficacy.
The hybrid delivery systems also led to an improvement in transfection efficiency. In addition, by modifying the surface charge of LNPs, they can be given targeting capability.
TNA delivery by lipodendriplexes, which are intricate systems that produced hybridization with the liposomal layers, is another developing delivery mechanism.
Lipid Polymer Hybrid Nanoparticle delivery – Video abstract [ID 198353]
Video Credit: Dove Medical Press/YouTube.com
Challenges and Limitations
LNPs are exciting non-viral carriers for genome drug carriers. Insufficient lysosomal release following LNP cell entrance is one of the significant outstanding challenges.
Another issue with LNPs is that their intravenous injection causes hepatic buildup where they are taken up by the renal systems.
As a result, when transitioning from in vitro models to in vivo investigations or preclinical studies, the transport effectiveness and clinical effects of conveyed nucleic acids may be reduced.
To summarize, TNAs are a promising treatment option for a wide spectrum of illnesses. Taking advantage of increased scientific interest in recent years, a slew of LNP-based nucleic acid drug carriers that can aid in the treatment of cancer, viral illnesses, heart disease, and hereditary abnormalities have emerged.
Several of these compositions have advanced to the drug trials phase or have even been licensed for usage in the public at large at unprecedented speeds. Nonetheless, these dosing methods are still in their adolescence, with the majority of them needing more rigorous investigation before proceeding from in vitro and in vivo tests to clinical testing.
Overall, development in generating targeted and sustained delivery carriers for effective cellular absorption is expected to accelerate tremendously.
Continue reading: The Potential of Plasmonic Nanoparticles in Biomedical Applications.
Niculescu, A. G., Bîrcă, A. C. & Grumezescu, A. M., (2021) New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery. Pharmaceutics, 13(12). 2053 Available at: https://www.mdpi.com/1999-4923/13/12/2053
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